Preventive effects of L-γ-Glutamylethylamide on lower urinary tract dysfunction induced by chronic sympathetic hyperactivity in rats

Matsuoka K1, Akaihata H1, Hakozaki Y1, Kirihana Y1, Natsuya H1, Kumekawa T1, Yoshioka S1, Makabe S1, Hasegawa A1, Onagi A1, Koguchi T1, Hata J1, Sato Y1, Kataoka M1, Kojima Y1

Research Type

Pure and Applied Science / Translational

Abstract Category

Overactive Bladder

Abstract 18
Live Pure and Applied Science 1 - Tiny Things for Big Effects
Scientific Podium Session 2
Thursday 14th October 2021
14:50 - 15:00
Live Room 1
Animal Study Overactive Bladder Prevention
1. Fukushima Medical University School of Medicine, Department of Urology
Presenter
Links

Abstract

Hypothesis / aims of study
Chronic sympathetic nervous system disorder leads to lower urinary tract dysfunction (LUTD) associated with overactive bladder (OAB), but underling mechanisms remain poorly understood. L-γ-glutamylethylamide (L-theanine), a glutamine derivative present in Japanese green tea, has recently gained attention for its sympathetic inhibitory effects. We speculated that L-theanine might suppress the development of LUTD associated with chronic sympathetic hyperactivity. This study therefore examined the effects of L-theanine on LUTD in spontaneously hypertensive rats (SHR), as a rat model of OAB with chronic sympathetic hyperactivity.
Study design, materials and methods
Twelve-week-old SHR were divided into a control groups (n=10) and an L-theanine group(n=10) that was given L-theanine solution to drink ad labium. After 6 weeks, both groups underwent cystometry and measurement of blood pressure and plasma catecholamine levels. Bladder tissue was harvested for pharmacological studies, histological examinations, and protein expression analyses. Contractile responses to 80-mM KCl, electrical field stimulation, 1-mM adenosine triphosphate (ATP), and carbachol in organ baths were recorded. As an evaluation of histological changes in the bladder, collagen-to-muscle (C/M) ratio in the smooth muscle layer and tunica media-to -internal lumen (M/L) ratio of small resistance vessels in the submucosal layer were measured. Malondialdehyde (MDA) and hypoxia-inducible factor (HIF)-1α were assessed as biomarkers for oxidative stress using immunohistochemical staining and western blotting. Values of p<0.05 were considered statistically significant.
Results
Bodyweight and bladder wet weights did not differ significantly between control (body weight: 353.0±12.3 g; bladder wet weight: 0.19±0.03 g) and L-theanine groups (354.0±11.3 g, p=0.70; 0.22±0.04 g, p=1.00, respectively). Mean blood pressure was significantly decreased in the L-theanine group (173.3±4.3 mmHg) compared with controls (159.9±3.3 mmHg, p=0.046). Serum noradrenaline level was significantly lower in the L-theanine group (365.5±31.6 pg/ml) than in controls (246.2±34.3 pg/ml, p=0.04). Cystometrograms showed that micturition interval and mean voided volume were significantly larger in the L-theanine group (7.8 ± 1.7 min and 1.3±0.35 ml, respectively) than in controls (5.6±8.4 min, p=0.002 and 0.96±0.18 ml, p=0.03, respectively). Contractile responses of bladder strips were significantly higher in the L-theanine group than in controls. C/M ratio, indicating the degree of fibrosis, was significantly lower in the L-theanine group than in controls (p=0.02). M/L ratio, indicating vascular resistance, was also significantly decreased in the L-theanine group than in controls (p=0.01). Although expression of HIF-1α did not differ significantly between groups, MDA expression was clearly decreased in the L-theanine group (p=0.03).
Interpretation of results
Our results suggest that ingestion of L-theanine for 6 weeks were effectively preserved lower urinary tract function in SHR. MBP depends on the vascular resistance of small arteries, which are responsible for providing a steady supply of blood to peripheral organs. The decreased MBP, reduced plasma noradrenaline concentrations, and decreased M/L ratio in bladder submucosa suggest that L-theanine suppressed chronic sympathetic hyperactivity and even improved peripheral vascular resistance. The evaluations of oxidative stress markers implied that L-theanine might improve LUTD by inhibiting oxidative stress pathways other than ischemia caused by chronic sympathetic hyperactivity.
Concluding message
L-theanine in Japanese green tea might prevent or ameliorate LUTD caused by chronic sympathetic hyperactivity by inhibiting oxidative stress pathways.
Disclosures
Funding none Clinical Trial No Subjects Animal Species Rat Ethics Committee The Animal Ethics Committee of Fukushima Medical University
03/11/2024 12:47:41